Candesarstad 16 mg Tabletten

CMDh/223/2005

February 2014

Public Assessment Report

Scientific discussion

Candesartan STADA 4, 8, 16, 32 mg Tabletten

Candesarstad 4, 8, 16, 32 mg Tabletten

(Candesartan cilexetil)

AT/H/0375/001-004

AT/H/0376/001-004

This module reflects the scientific discussion for the approval of Candesartan STADA/

Candesarstad. The procedure was finalised at 27.07.2011/ Day 196. For information on changes

after this date please refer to the module ‘Update’.

I.

INTRODUCTION

Based on the review of the data and the Applicant’s response to the questions raised by RMS and

CMSs

quality,

safety

efficacy,

AGES

(Austrian

Competent

Authority)

granted

Stada

Arzneimittel GmbH, Vienna, a marketing authorisation for Candesartan STADA 4, 8, 16, 32 mg

tablets and Candesarstad 4, 8, 16, 32 mg tablets in the treatment of

Essential hypertension

Treatment of patients with heart failure and impaired left ventricle systolic function (left

ventricular ejection fraction

40%) as add-on therapy to ACE

inhibitors or when ACE-

inhibitors are not tolerated.

The product is a prescription only medicine.

II.

QUALITY ASPECTS

II.1

Introduction

Candesartan STADA/ Candesarstad is a tablet which is presented in a PVC-PVDC/Alu blister.

II.2

2.2

Drug Substance

The active substance in Candesartan STADA/ Candesarstad is Candesartan cilexetil. The specification

of the active substance meets the current scientific requirements. The adequate quality of the active

substance has been shown by submitting the appropriate control data. The stability of the active

substance has been tested under ICH conditions. The results of the stability studies support the

established retest-period.

II.3

Medicinal Product

Candesartan STADA/ Candesarstad contains the following excipients:

Lactose monohydrate (133.80/129.80/121.80/243.60 mg Lactose monohydrate for Candesartan

STADA/ Candesarstad 4/8/16/32 mg tablets, respectively), Maize starch, Hydroxypropylcellulose,

Croscarmellose sodium, Magnesium stearate, Triethyl Citrate.

The manufacturers responsible for batch release are

For Candesartan STADA:

STADA Arzneimittel AG, 61118 Bad Vilbel, Germany;

Stada Arzneimittel GmbH, 1190 Wien, Austria;

Centrafarm Services B.V., 4879 AC Etten Leur, The Netherlands;

Eurogenerics N.V., 1020 Brussels, Belgium;

LAMP SAN PROSPERO S.p.A., 41030 San Prospero (Modena), Italy;

Siegfried Generics Malta Ltd., Hal Far BBG3000, Malta.

For Candesarstad:

STADA Arzneimittel AG, 61118 Bad Vilbel, Germany;

Centrafarm Services B.V., 4879 AC Etten Leur, The Netherlands;

Siegfried Generics Malta Ltd., Hal Far BBG3000, Malta;

ALIUD PHARMA GmbH, 89150 Laichingen, Germany;

Clonmel Healthcare Ltd, Clonmel, Co. Tipperary, Ireland.

The development of the product has been sufficiently made and deemed appropriate. The usage of all

the excipients has been described.

The release specification includes the check of all parameters relevant to this pharmaceutical form.

Appropriate data concerning the control of the finished product support the compliance with the

release specifications.

The packaging of the medicinal product complies with the current legal requirements.

Stability studies under ICH conditions have been performed and data presented support the shelf life

claimed in the SmPC, with a shelf life of 36 months when stored below 25°C.

The pharmaceutical quality of Candesartan STADA/ Candesarstad has been adequately shown.

II.4

Discussion on chemical, pharmaceutical and biological aspects

Information on development, manufacture and control of active substance and medicinal product has

been presented in a satisfactory manner. The results of tests carried out indicate satisfactory

consistency and uniformity of important product quality characteristics.

III.

NON-CLINICAL ASPECTS

Pharmacodynamic, pharmacokinetic and toxicological properties of Candesartan cilexetil are well

known. As Candesartan cilexetil is a widely used, well-known active substance, the applicant has not

provided additional studies and further studies are not required. An overview based on literature

review is, thus, appropriate.

The non-clinical overview has been written by an appropriately qualified person and is a suitable

summary of the non-clinical aspects of the dossier.

An Environmental Risk Assessment has not been provided and one is not required for an application

of this type.

The SmPC and PIL are consistent with those for the reference product, harmonised in an Article 30

Referral (16

of July 2010), where appropriate.

From a non-clinical point of view it is recommended that marketing muthorisations are granted for

these applications.

IV.

CLINICAL ASPECTS

IV.1

Introduction

The applicant has submitted two single dose bioequivalence studies performed with the highest and

the lowest strength (32mg and 4mg) under fasting conditions. A biowaiver for the 8mg and 16mg

strengths was claimed by the applicant.

IV.2

Pharmacokinetics

In both studies the results for the primary pharmacokinetic parameters (AUC

and C

) indicated that

the 90% confidence intervals test/reference ratio of geometric means for candesartan lie within the

acceptance range of 80.00 - 125.00%. Thus, bioequivalence has been shown between the test and

reference products in these studies.

As the 8mg and 16mg strength products meet all the biowaiver criteria as specified in the Guideline on

the Investigation of Bioequivalence (CPMP/EWP/QWP/1401/98 Rev. 1/ Corr *), the results and

conclusions of the bioequivalence studies can be extrapolated to the 8mg and 16mg tablets.

IV.3

Pharmacodynamics

With the exception of the bioequivalence studies, no new pharmacokinetic or pharmacodynamic data

were submitted with these applications and none were required.

IV.4

Clinical efficacy

With the exception of the data submitted during the bioequivalence studies, no new safety data were

submitted and none were required. No new or unexpected safety concerns were raised during the

bioequivalence studies.

IV.5

Clinical safety

With the exception of the data submitted during the bioequivalence studies, no new safety data were

submitted and none were required. No new or unexpected safety concerns were raised during the

bioequivalence studies.

IV.6

Discussion on the clinical aspects

The clinical overview has been written by an appropriately qualified person and is a suitable summary

of the clinical aspects of the dossier.

The SmPC and PIL are consistent with those for the reference product, harmonised in an Article 30

Referral (16

of July 2010), where appropriate.

Based on the submitted bioequivalence studies the test product is considered bioequivalent with the

reference product Amias 4mg / 8mg / 16mg / 32mg tablets by Takeda Ltd UK.

From a clinical point of view it is recommended that marketing authorisations are granted for these

applications.

V.

OVERALL CONCLUSION, BENEFIT/RISK ASSESSMENT AND

RECOMMENDATION

The pharmaceutical quality of Candesartan STADA/ Candesarstad has been adequately shown.

The benefit risk assessment is considered positive.

User consultation

package

leaflet

been

evaluated

user

consultation

study

accordance

with

requirements of Articles 59(3) and 61(1) of Directive 2001/83/EC. The language used for the purpose

of user testing the PIL was English.

The results show that the package leaflet meets the criteria for readability as set out in the Guideline

on the readability of the label and package leaflet of medicinal products for human use.

Public Assessment Report

Update

Candesartan STADA 4, 8, 16, 32 mg Tabletten

Candesarstad 4, 8, 16, 32 mg Tabletten

(Candesartan cilexetil)

AT/H/0375/001-004

AT/H/0376/001-004

This module reflects the procedural steps and scientific information after the finalisation of the

initial procedure.

Bundesamt für Sicherheit im Gesundheitswesen

Schnirchgasse 9 l A-1030 Wien l www.basg.at l www.ages.at

DVR: 2112611 l Konto Nr.: 50670 871 619 l BLZ: 12000 l IBAN: AT97 1200 0506 7087 1619 l BIC/SWIFT: BKAUATWW

Procedure

number*

Scope

Product Information

affected

Date of end

of procedure

Approval/

non approval

Summary/ Justification for

refuse

AT/H/0375-

376/001-

004/II/001

Introduction of a new manufacturer of the active substance that is supported by an

ASMF

21.06.2012

Approved

N.A.

AT/H/0375-

376/001-

004/R/001

Renewal of the marketing authorisation

08.09.2016

Approved

N.A.

*Only procedure qualifier, chronological number and grouping qualifier (when applicable)